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A phase II clinical trial of intravesical YH01 for BCG-unresponsive high-risk non–muscle-invasive bladder cancer (NMIBC).

e16612 Background: Non–muscle-invasive bladder cancer (NMIBC) accounts for approximately 70–80% of bladder cancer cases. Nearly 45% of high-risk patients experience recurrence or progression within one year after Bacillus Calmette-Guérin (BCG) therapy and develop BCG-unresponsive disease. YH01 is a recombinant oncolytic adenovirus with modified capsid proteins to enhance tumor targeting and oncolytic activity in BCG-unresponsive disease. Methods: This open-label, multicenter Phase II trial was conducted in two stages (Phase IIa and IIb). All subjects received intravesical instillation of 75 mL YH01 injection (1×10¹⁰ IFU/mL) per dose. Phase IIa included three treatment groups: ① Treatment Group 1: Induction instillation 1-3 times (once weekly for the first 1-3 weeks), and maintenance instillation (once during the first week of each cycle); ② Treatment Group 2: Induction instillation 4-6 times (once weekly for the first 4-6 weeks), maintenance instillation protocol identical to Group 1; ③ Treatment Group 3: Induction instillation 6 times (once weekly for the first 6 weeks), consolidation instillation 3 times (once every 2 weeks for the first 6 weeks), maintenance instillation 3 times (once every 4 weeks), followed by once every 12 weeks. Patients in Groups 2 and 3 with recurrence could receive a second course of induction instillation. Results: A total of 13 patients were enrolled at this center in Phase IIa (with a median follow-up of 9.4 months), distributed across all three treatment groups. Efficacy outcomes: Group 1 (n = 3), 1 patient recurred, 1 progressed, and 1 achieved Complete Response (CR). In Group 2 (n = 3), 1 patient recurred and 2 achieved CR. In Group 3 (n = 7), all patients (100%) achieved CR. The overall response rate (ORR) was 76.9%. Safety results: A total of 61 adverse events (AEs) were reported, of which 67.2% were Grade 1 and 32.8% were Grade 2. Grade 2 AEs occurred in 8 patients (61.54%). The most common Grade 1 AEs included increased urinary white blood cell count, hematuria, anemia, and decreased lymphocyte count. The most frequent Grade 2 AE was urinary tract infection (9 events), followed by hyperbilirubinemia and increased urinary white blood cell count. No Grade 3 or higher AEs were observed, and the overall safety profile was favorable and manageable. Conclusions: Following dose-exploration, Group 3 achieved a 100% complete response (CR) rate. These findings suggest that intravesical YH01 injection demonstrates promising preliminary efficacy and a favorable safety profile for BCG-unresponsive or failed intermediate/high-risk NMIBC. YH01 represents a viable novel alternative for patients who are ineligible for or refuse radical cystectomy.

Atomic‐Scale Understanding of Selectivity Control in Nitrate Reduction on Cu(100) Under Acidic and Alkaline Conditions

ABSTRACT We investigate the nitrate reduction reaction (NO 3 RR) on the Cu(100) surface using grand‐canonical density functional theory (GC‐DFT) under constant electrode potential. Ionic correction schemes are applied to both reactants and products to ensure an accurate representation of their physical states, and gas‐phase reference error corrections are included to address known limitations of the generalized gradient approximation (GGA) in DFT simulations. The role of pH in modulating the binding energies of key intermediates and transition states governing the elementary steps of nitrate conversion is analyzed as a function of applied electrode potential. To validate the computational approach, DFT‐based molecular dynamics simulations with explicit water molecules and activation energy calculations for proton–electron transfer steps are performed. Based on the modeling framework and computational strategy presented here, the results show that under acidic conditions, NO 3 RR on Cu(100) favors the formation of nitric oxide and ammonium at cathodic potentials ( U RHE < 0.1 V), whereas under alkaline conditions at comparable potentials, nitrite and hydroxylamine dominate. These findings are consistent with experimentally reported potential‐ and pH‐dependent selectivity trends and suggest that the approach provides a general computational framework for modeling pH‐dependent electrocatalytic reactions and predicting potential‐dependent selectivity.

Advanced real sample monitoring and density functional theory insights into plastic waste-derived carbon dots for detection of toxic environmental contaminants

First-in-class HIV drug nabs approval

High‐Density Co–Ir–Co Triple‐Atom Sites in Salphen‐Fused Nanoribbons Break the Activity‐Stability Dilemma in Alkaline Oxygen Evolution

ABSTRACT The development of stable, active, and well‐defined electrocatalysts for water oxidation is vital for large‐scale green hydrogen production. However, the inherent trade‐off between activity and stability of electrocatalysts imposes fundamental limitations on their practical applications. Herein, we fabricated a molecularly precise triatomic catalyst featuring highly dispersed atomic iridium (14.3 wt.%) along with dense atomic cobalt grippers (10.4 wt.%) anchored on a Salphen‐fused nanoribbon (Co 2 Ir‐SNR), enabling highly effective and durable oxygen evolution reaction (OER). In situ infrared spectroscopy together with theoretical calculations reveals that the Co 2 Ir‐SNR follows the infrequent oxide path mechanism (OPM) with a reduced energy barrier, where the active iridium sites confined in two cobalt grippers promote direct O−O radical coupling for O 2 evolution. Consequently, the triatomic catalyst achieves a remarkable overpotential of 212 ± 3 mV at 10 mA cm −2 and possesses durability with stable operation for up to 1000 h at an ampere‐level current density under alkaline conditions. This work presents a viable strategy to break the activity‐stability dilemma encountered in OER, providing crucial guidance for developing catalysts that withstand the stringent requirements of industrial hydrogen production.

Liquids as Reinforcements for Anisotropic and Tough Soft Matter Composites

ABSTRACT Biological tissues and engineered composites achieve exceptional mechanical properties through microstructures that create stiffness and toughness in preferred directions. While composites traditionally leverage solid reinforcements to drive this anisotropy, directional mechanics in all‐soft matter composites remain a longstanding challenge, despite their importance for soft devices that stretch and adapt under load. Here, we create all‐soft matter composites where liquid inclusions direct and enable anisotropic and heterogeneous mechanical properties. By shaping and orienting liquid metal droplets within elastomers, we program directional stiffness, enhance toughness beyond 36,000 J m −2 , and guide cracks along non‐linear paths with deflections up to 150 during extreme deformations. This allows liquids, which are up to a million times softer than traditional rigid inclusions, to act as mechanical reinforcements. These liquid inclusions enhance directional stiffness or softness relative to unfilled elastomers and enable programmable crack‐path engineering that surpasses simple blunting or trapping, with anisotropy tuned on demand during processing. We leverage this to protect soft circuits even under catastrophic damage, offering new possibilities to direct mechanical forces in compliant materials for resilient soft electronics and robots, wearables, and morphing matter.

High-intensity focused ultrasound (HIFU) modeling: in vitro validation and integration into patient-specific planning tool

Structural basis for the mechanism and stability of the EEPD1 5′ endonuclease

Multi-exposure environmental mapping and scale effects in lung cancer risk assessment: An ecological synthesis from central Argentina.

e22582 Background: Lung cancer is a major public health burden and, beyond tobacco smoking, its risk may be influenced by modifiable environmental exposures. Residential radon and arsenic in drinking water are Group 1 carcinogens (WHO/IARC) associated with increased lung cancer risk. In Córdoba Province, central Argentina, published studies at different spatial scales allow joint examination of these exposures and the spatial distribution of lung cancer. We integrated this evidence to inform prevention priorities and to discuss limitations due to spatial scale mismatch. Methods: We conducted a broad spatial integration of published data on residential radon, groundwater arsenic content and lung cancer, considering ecological inference and the modifiable areal unit problem. Results: Residential radon measured in the western and northwestern Córdoba Pampean Ranges (dominated by metamorphic and granitic rocks) showed strong micro-scale variability (6–307 Bq/m³; mean ~46); and about 6% exceeded the WHO reference level (100 Bq/m³). Concentrations were lower in warmer months and higher in below-ground rooms, with exceedances concentrated in granitic settings and areas affected by active fault systems. Groundwater arsenic showed a macro-regional pattern across the province, with the highest concentrations in the southern and southeastern lowland plains and generally lower levels in the western and northwestern mountains. Registry-based analyses identified 8,246 lung cancer cases diagnosed during 2004–2014 (ages 35–84) and significant department-level spatial clustering, with hotspots in the eastern and southeastern departments and lower case concentration in the northwest. The arsenic regional gradient qualitatively resembled the cancer hotspot pattern. Radon information still remained highly localized, thus an ecological epidemiological approach cannot be applied in the identified high-radon areas. Conclusions: This ecological integration of published evidence suggests qualitative spatial concordance between elevated groundwater arsenic and higher lung cancer burden in eastern and southeastern Córdoba. Residential radon shows strong local and seasonal variability, limiting comparison with large-area disease maps without standardized long-term measurements. Strengthening exposure monitoring can improve population-level risk assessment and guide prevention planning.

Phase 1 faecal microbiota transplantation in patients with advanced pancreatic carcinoma (FMTPanc Trial).

TPS4262 Background: Higher abundance of specific oral, pancreatic and/or gut microbes is correlated with pancreatic cancer occurrence (e.g. Porphyromonaas gingivalis , Malassezia sp.). Furthermore, the pancreatic tumour microenvironment of long-term survivors (≥ 5 years) shows richer tumoral microbial diversity associated with more active T-cells and fewer immune-suppressing cells than short-term survivors. Preclinical animal studies have also demonstrated that faecal microbiota transplantation (FMT) from a healthy donor or a long-term survivor can significantly decrease the size of pancreatic tumours. These findings demonstrate that manipulations of the gut and/or organ microbiota holds promise as part of cancer treatment. This trial aims to evaluate whether restoring a healthier microbiota can improve symptoms, visceral pain and treatment efficacy in people with non-resectable pancreatic cancer. Methods: This study is a Phase 1 double-blind randomised placebo-controlled trial (RCT) assessing the safety and potential benefit of oral FMT in patients with non-resectable pancreatic cancer. FMT will be a co-treatment to the standard of care chemotherapy. The primary outcomes are FMT safety and toxicity and mortality at 3, 6, and 12 months after chemotherapy initiation. Secondary outcomes include: changes in visceral pain and symptoms measured by PAGI-SYM, changes from baseline in blood CA-19-9 levels and reduction in tumour size as surrogate marker of treatment efficacy, and changes in faecal microbiota as a surrogate marker of gut flora restoration and treatment efficacy at 3, 6, and 12 months after treatment initiation. Power calculations were conducted for the main secondary clinical outcome of interest (i.e. the PAGI-SYM tool) that encompasses pain and symptom monitoring using published evidence, an MCID of 0.94, for an alpha of 0.05 and 80% power a minimum of 14 participants per arm is required. The trial aims to recruit a minimum of 28 and maximum of 60participants, 14-30 per arm. Eligible patients will have advanced and unresectable adenocarcinoma of the pancreas suitable for standard chemotherapy (gemcitabine/nab-paclitaxel or FOLFIRINOX) and be treatment-naive. Patients will be randomised 1:1 to FMT or placebo. FMT and placebo capsules will be prepared by BiomeBank (Adelaide South Australia). Stool will be sourced from healthy donors and rigorously screened following criteria specified by the Australian Therapeutic Administration (TGA). FMT/placebo will be provided through two doses (dose 1: 25mg, dose 2: 50mg). Chemotherapy will commence 3 to 14 days after completion of the first FMT dose (week 0). Supportive medication includes pancrelipase (2x25,000U three times a day) to facilitate digestion during FMT treatment. The FMTPanc is open at 3 sites across South Australia and Victoria and as of January 2025 12 patients have been enrolled. Clinical trial information: ANZCTR: ACTRN12624000455561.

Inpatient financial toxicity among women hospitalized with breast cancer in the United States, 2013–2022.

1555 Background: Financial toxicity is an increasingly recognized consequence of cancer care. While the outpatient costs of breast cancer are well described, national trends and drivers of inpatient financial toxicity are not well understood. We evaluated temporal trends in hospitalization volume, inflation-adjusted inpatient charges, and factors associated with high financial toxicity among women hospitalized with breast cancer in the United States. Methods: We performed a retrospective analysis of the National Inpatient Sample (2013–2022), including women aged ≥18 years with a breast cancer diagnosis. Survey weights, strata, and clusters were applied. Charges were inflation-adjusted to 2022 USD. High financial toxicity was defined as inpatient charges ≥75th percentile. Temporal trends were assessed using weighted regression, and multivariable survey-weighted logistic regression identified predictors of high financial toxicity. Results: An estimated 1.70 million weighted hospitalizations were identified. Annual hospitalizations declined significantly (P for trend <0.001), from 178,660 in 2013 to 168,630 in 2022, with a nadir in 2020. In contrast, mean inflation-adjusted inpatient charges increased by 35.5%, from $58,869 to $79,797 (P for trend <0.001), totaling more than $119.3 billion in cumulative charges. Most hospitalizations occurred at urban teaching hospitals (71.2%). On multivariable analysis, urban teaching (OR 3.84, 95% CI 3.58–4.12) and urban non-teaching hospitals (OR 3.53, 95% CI 3.28–3.79) had nearly four-fold higher odds of high financial toxicity compared with rural hospitals. Compared with White patients, Hispanic (OR 1.53), Asian/Pacific Islander (OR 1.44), and Black patients (OR 1.10) had higher odds. Private insurance (OR 1.14) and residence in the highest income quartile (OR 1.35) were associated with increased odds, while older age was associated with lower odds. Odds of high financial toxicity increased steadily over time, peaking in 2020 (OR 1.58) (P for trend <0.001). Conclusions: Despite declining hospitalization rates, inpatient financial toxicity among women with breast cancer has worsened substantially, driven primarily by hospital setting and structural factors. Racial and ethnic disparities were also evident, with minority groups experiencing higher odds of high inpatient charges. These findings underscore the need for value-based strategies and policy interventions to mitigate inpatient financial burden in oncology care.

Disaggregated lung cancer mortality trends in Asian American, Native Hawaiian, and Pacific Islander (AANHPI) patients by key sociodemographic features including sex, age, and smoking status.

8593 Background: Lung cancer is a leading cause of death in AANHPI populations, yet studies aggregate patients with diverse cultural backgrounds and immigration histories into an “Asian American” monolith, obscuring high-risk subgroups. Prior national disaggregation work has not captured key demographic variables important to understanding epidemiologic trends. Methods: This study analyzed the US Multiple Cause of Death database for deaths from lung cancer from 2018–2023, sociodemographic information included age at death, sex, race/ethnicity, smoking status, and education. Disaggregated AANHPI subgroup trends were evaluated using ACS 1-year estimates; other analyses used CDC WONDER bridged-race populations. Joinpoint estimated annual percent change in mortality(APC)/AdjustedAPC by race and sex. Pearson's Chi-squared test tested comparisons. Results: From 2018-2023, there were 430,703 deaths due to lung cancer in males, of which 2.7% (n=11,441) were in AANHPI males; there were 379,199 deaths in females, of which 2.5% (n=9397) were in AANHPI females. There were demographic differences in deaths within AANHPI subgroups and compared against white patients. For example, 0.5% of deaths in white male and females occurred in those aged 25-44, but this younger age group had 2.1% (male) and 4.3% (female) of Indian American deaths and 1.2% (male) and 1.7% (female) of Chinese American deaths. Deaths in white patients were associated with smoking in 48% (male) and 43% (female) of cases, but in far less of Chinese American (17% male, 4.4% female) and Filipino American (21% male, 9.7% female) lung cancer deaths (p<0.001 comparison). From 2018–2023, adjusted AANHPI male lung cancer mortality significantly declined −1.63% (95% CI −1.87 to −1.38; p<0.0001) but this was not seen AANHPI females (AAPC −1.20%; −2.86 to 0.79; p=0.22). The magnitude of AANHPI mortality decreases were smaller than in White (male -3.95, -4.43 to -3.24, female -2.35, -3.64 to -1.10; p<0.0001 both) and Black (male -4.35, -5.22 to -3.52, female -2.99, -3.99 to -2.96) adults during the same time period (p<0.0001 both). Disaggregation showed rising lung cancer mortality in Filipino women (AAPC +1.99%; 95% CI 0.59–3.54; p=0.006) and upward trends in Vietnamese women (AAPC +2.29%; 95% CI −1.05 to 5.81), whereas most AANHPI men had stable or modestly declining mortality. Conclusions: Despite large gains in lung cancer mortality over time, AANHPI populations —especially AANHPI women— show slower improvements despite high never-smoker prevalence, underscoring the need for disaggregated research. Rising lung cancer mortality in specific unique populations like Filipino women should motivate further research and guide targeted community outreach so that all populations benefit from improvements in early diagnosis and precision oncology.

Wire-guided versus radio-guided localization for non-palpable occult lesion in breast tissue: A systematic review and meta-analysis.

579 Background: Accurate preoperative localization of non-palpable breast lesions is crucial for successful breast-conserving surgery. Wire-guided localization (WGL) has traditionally been the standard technique; radio-guided localization (ROLL) has emerged as an alternative approach with potential benefits in surgical precision and workflow. Current evidence comparing the efficacy and safety of these two techniques remains inconsistent. This systematic review and meta-analysis evaluates WGL versus ROLL for non-palpable breast lesions with respect to surgical and oncological outcomes. Methods: A systematic literature search was conducted on electronic databases from inception until January 2026. Outcomes included re-excision rates, margin involvement, specimen volume and weight, accurate localisation of lesions and operative time. We employed risk ratios (RRs) with 95% Confidence Intervals (CIs) for dichotomous outcomes. Mean differences (MDs) or standardized mean differences (SMDs) with 95% CIs were computed for continuous outcomes using Review Manager V.5.4. Quality assessment and risk of bias were assessed using the Cochrane Risk of Bias Tool 2 on all included RCTs. Results: This systematic review and meta-analysis included 13 studies with a total of 5,318 patients. There was no statistically significant difference in the re-excision rates between the two interventions (OR = 1.44; 95% CI: [0.73, 2.83], p = 0.143). Localization time (SMD = 1.75; 95% CI: [-1.01, 4.51], p = <0.0001) and length of operation time was significantly shorter in the ROLL group (SMD = 0.22; 95% CI: [0.10, 0.34], p = 0.028). There was no statistically significant difference in the margin involvement between the two groups (OR = 0.61; 95% CI: [0.37, 0.99], p = 0.063). ROLL was associated with significantly smaller volume of specimen (SMD = 0.16; 95% CI: [-5.41, 5.73], p = <0.0001). Conclusions: ROLL and WGL demonstrate comparable oncological outcomes, with no significant differences in the re-excision rates or margin involvement. However, ROLL is associated with significantly shorter localization and operative times, suggesting procedural efficiency over WGL.

Epidemiologic trends and risk factor transitions in adolescent and young adult lung cancer in East Asia, 1990–2023.

e22587 Background: East Asia bears the highest global burden of adolescent and young adult (AYA) lung cancer. Updated regional assessments capturing recent epidemiologic trends and evolving risk-factor structures are limited. Methods: Using the Global Burden of Disease 2023, we report incidence rate (IR) and mortality rate (MR) per 100,000, and risk-factor–attributable mortality for AYA lung cancer (ages 15–49) from 1990–2023 in China, Japan, South Korea, North Korea, Taiwan, Mongolia, and globally, stratified by sex. Results: In 2023, IRs in all East Asia countries exceeded the global average (3.2). IR was highest in Taiwan (6.1), North Korea (5.9), and China (5.8), and lowest in Japan (3.2) and South Korea (3.4). IR was highest in Mongolia (7.3) in males and Taiwan (5.5) in females. From 1990–2023, IR declined globally (−24%) and in Japan (−29%) but increased in Taiwan (35%). In males, IR decreased globally (−30%), in Japan (−37%), and South Korea (−40%); but increased in Mongolia (88%) and Taiwan (6.8%). In females, IR increased in North Korea (94%) and Taiwan (53%). In 2023, MRs exceeded the global average (2.45 per 100,000) in North Korea (4.8), China (4.4), Taiwan (4.4), and Mongolia (4.1), but remained lower in Japan (1.8) and South Korea (2.0). MR was highest in Mongolia (6.1) for males and North Korea (3.9) for females. From 1990–2023, MR declined globally (−27%), in Japan (−44), and South Korea (−46%) but increased in Taiwan (22%). In males, MR decreased globally (−32%), in Japan (−49%), and South Korea (−55%) but increased in Mongolia (87%). In females, MR decreased in Japan (−33%) but increased in North Korea (87%) and Taiwan (34%). In 2023, 78–84% of male and 44–62% of female deaths were attributable to modifiable risks. Tobacco accounted for 63–74% of male deaths and 23–43% of female deaths. Smoking increased in China and Mongolia in males and decreased in Japan and South Korea. Secondhand smoke decreased in Japan, South Korea, and Taiwan in females. Air pollution accounted for 7.7–39% of deaths with mortality mainly from ambient particulate matter except in North Korea, where household solid fuels accounted for 31–35% of deaths. Overall air pollution declined or stabilized, but ambient particulate matter increased markedly in China (137–220%) and Mongolia (267–263%). Occupational carcinogens accounted for 4.7–12% of deaths and increased from 1990–2023 in all countries except Japan and South Korea. High fasting plasma glucose related deaths increased in Mongolia and Taiwan. Conclusions: AYA lung cancer trends in East Asia vary widely by country and sex. Only Japan and South Korea had declines in mortality rates, coinciding with reduced male tobacco-attributable mortality, while other countries had stagnant or increasing burden. Urgent policy measures must strengthen tobacco control and address environmental, occupational, and metabolic risks to reduce preventable deaths.

More than follow-up: Outcomes from an integrated cancer survivorship wellness clinic.

e13796 Background: Studies have identified persistent gaps in survivorship care coordination, particularly fragmented communication with primary care providers (PCPs) during and after cancer treatment. As a result, many survivors disengage from primary care despite ongoing needs related to late effects, health promotion, and preventive screening, while PCPs report limited confidence in providing care to cancer survivors. To address these gaps, an advanced practice provider (APP)–led Survivorship Wellness Clinic (SWC) was established to deliver personalized, evidence-based survivorship care and care plans, proactively identify and refer patients for symptom management; support lifestyle modification; and strengthen coordination and collaboration with PCPs. Methods: We prospectively collected data on all patients seen in SWC from February 2023 to December 2025, including demographics, symptom burden, PCP access status, lifestyle recommendations, cancer screening and surveillance, and referrals to supportive oncology care or other specialty clinics. Descriptive statistics were used to summarize outcomes. Results: A total of 329 patients were seen at baseline; 45 completed the first follow-up visit (median time 366 days). The cohort was predominantly female (76%) and White (80%), with 55% identifying as Hispanic/Latino. The most common cancer types were breast (60%), gastrointestinal (13%), and genitourinary (10%). At baseline, 12% lacked a PCP, and 95% of these were subsequently referred to one. Most patients (85%) received at least one lifestyle modification recommendation (exercise: 82%, nutrition: 82%). Seventy-five percent reported at least one treatment-related side effect, most commonly fatigue (21%), peripheral neuropathy (14%), and arthralgias (12%). To address treatment-related side effects and unmet needs, 57% of patients received referrals to various supportive care services. The highest referrals were nutrition (31%), exercise (30%), and massage therapy (22%). Additionally, referrals to specialists were provided for 34%, with psychology (8%) and sexual health (7%) being the most common. Cancer screenings were ordered for most patients, with follow-up compliance rates ranging from 63% to 96%, depending on screening type. Among follow-up patients, 93% visited a PCP after SWC, and 45% discussed their survivorship care plan with their PCP. Conclusions: This large analysis, with follow-up data, underscores the need for survivorship clinics, particularly in lifestyle modification, care coordination, and PCP engagement. These descriptive findings highlight the feasibility and importance of implementing survivorship programs and suggest potential benefits in bridging gaps between oncology and primary care. Further research is needed to evaluate long-term outcomes and comparative effectiveness.

Metastatic pancreatic cancer in elderly patients.

e16347 Background: Elderly patients are underrepresented in clinical trials, and real-world data on treatment patterns and outcomes in this population are limited. We aimed to assess treatment patterns, survival outcomes, and the role of performance status in treatment selection among patients aged ≥70 years with metastatic pancreatic cancer. Methods: We conducted a retrospective chart review of patients aged ≥70 years diagnosed with metastatic pancreatic cancer at our institution between 01/01/2013 and 12/31/2023. The primary endpoint was overall survival from diagnosis. Secondary endpoints included variables such as treatment utilization, next-generation sequencing (NGS) test rates, and palliative care referral patterns. Results: Mean age at diagnosis was 75.1 years (standard deviation (SD) 4.4); 68.3% were male. Race was 85.4% Caucasian, 2.4% Black, and 12.2% other; 7.3% were Hispanic. ECOG was most commonly 1 (17/41, 41.5%). The liver was the most common metastatic site (31/41, 75.6%), followed by lungs (13/41, 31.7%). Prior localized non-pancreatic cancer was present in 24.4% (10/41), there were no prior metastatic diseases. Pathologic confirmation occurred in 92.7% (38/41), and 58.5% (24/41) received systemic therapy, initiated a mean 21.1 days post-diagnosis (SD 18.0). Among treated patients, FOLFIRINOX was most common (13/24, 54.2%). Second-line therapy was given in 50% (12/24), and third-line in 25% (6/24). Among treated patients, 75% (18/24) had ECOG ≤2; 25% (6/24) undocumented. Among untreated patients, 35.3% (6/17) had ECOG ≤2, 29.4% (5/17) ECOG ≥3, and 35.3% (6/17) undocumented. Surgical or minimally invasive procedures were performed in 31.7% (13/41), most commonly biliary stenting/drainage (76.9%, 10/13). NGS was performed in 17% (7/41), including one patient before 2019 and the remainder in or after 2019; among treated patients, 25% (6/24) underwent NGS. Median time from diagnosis to death was 98 days (Interquartile Range (IQR) 35-369), compared with 185 days (IQR 75.5-486) in treated patients and 29.5 days (IQR 17.3-64.3) in untreated patients, a statistically significant difference (p = 0.0003; hazard ratio 0.3, 95% Confidence Interval 0.1–0.8). Only 48.8% (20/41) were referred to palliative care; death data were unavailable for 12 patients due to loss to follow-up or relocation, and these patients were censored at last follow-up. Conclusions: In this real-world cohort, elderly patients with metastatic pancreatic cancer who received systemic therapy had significantly longer survival than those who did not, consistent with potential treatment benefit in those with reasonable performance status. In patients diagnosed in or after 2019, only 6/25 had NGS, and palliative care referrals were also underutilized, representing quality improvement opportunities. No treated patient had ECOG ≥3, while nearly a third of untreated had ECOG ≥3, indicating performance status strongly influenced treatment decisions.

A phase II study evaluating treatment discontinuation of dual anti-HER2 therapy in metastatic HER2-positive breast cancer after five years of sustained complete response (FREEDOME-trial).

TPS1143 Background: Dual anti-HER2 therapy with trastuzumab (T) and pertuzumab (P) has transformed outcomes in HER2-positive metastatic breast cancer (mBC), with approximately 20% of patients maintaining response beyond 8 years based on CLEOPATRA trial data. Current practice continues anti-HER2 therapy indefinitely in responding patients, despite lack of evidence supporting necessity of lifelong treatment in long-term responders. This approach is associated with cumulative financial burden, and quality of life impact from indefinite therapy requirements. No prospective data exist regarding optimal duration of anti-HER2 therapy in long-term responders, nor are there validated biomarkers to guide treatment discontinuation decisions. Minimal residual disease (MRD) assessment has shown promise in other malignancies for identifying patients at low risk of recurrence. This study addresses an unmet need for evidence on safety of treatment discontinuation in long-term responders. Methods: This prospective, multicenter, single-arm phase II trial enrolls patients with HER2-positive mBC who have maintained CR for ≥5 years on dual anti-HER2 therapy (T plus P). Target enrollment is 40 patients based on Fleming's single-stage design to detect median progression-free survival (mPFS) >12 months with 80% power (α=0.05). Key eligibility criteria include: confirmed HER2-positive mBC, sustained CR by RECIST 1.1 for ≥5 years, normal tumor markers (CA125, CEA, CA15-3), and no evidence of progression on baseline PET-CT. Patients with concurrent malignancies requiring systemic therapy are excluded. Following enrollment, participants discontinue T+P therapy but should continue endocrine therapy (if given). Surveillance includes PET-CT at baseline, 3, 6, 12 months, then annually; annual mammography/ultrasound per institutional standards; and blood collection for tumor markers at baseline, 3, 6, 12 months, then annually. Patients resuming anti-HER2 therapy upon progression remain on study for survival assessment. Primary endpoint is mPFS post-discontinuation. Secondary endpoints include 6-month PFS, 12-month PFS, and median overall survival. Exploratory analyses examine tumor markers as predictive biomarkers. Kaplan-Meier methodology will estimate survival probabilities with 95% confidence intervals. As of January 2026, one site is open for recruitment. Minimal residual disease analysis is planned and will be submitted to the IRB committee for approval. Study completion is anticipated by 2031 with interim analysis planned after 2 years. Clinical trial information: MOH_2025-12-27_015564.

Overall survival subgroup analyses for prior taxane use in the phase 3 ROSELLA trial of relacorilant plus nab-paclitaxel versus nab-paclitaxel monotherapy in patients with platinum-resistant ovarian cancer (GOG-3073, ENGOT-ov72, APGOT-Ov10, LACOG-0223, and ANZGOG-2221/2023).

5503 Background: Relacorilant is a first-in-class, selective glucocorticoid receptor antagonist that increases tumor sensitivity to chemotherapy-induced apoptosis. The phase 3 ROSELLA trial of relacorilant plus nab-paclitaxel in patients with platinum-resistant ovarian cancer (PROC) recently reported statistically significant results for the dual primary endpoints of progression-free survival (PFS) and overall survival (OS). The relacorilant combination was well tolerated and the safety profile was similar to nab-paclitaxel monotherapy. Here we present final OS subgroup analyses for prior taxane use. Methods: Patients (n = 381) were randomized 1:1 to relacorilant (150 mg PO the day before, of, and after nab-paclitaxel) plus nab-paclitaxel (80 mg/m 2 IV on days 1, 8, and 15 of each 28-day cycle) or nab-paclitaxel alone (100 mg/m 2 IV on the same schedule). The final OS analysis was performed after 288 deaths had been reported (76% maturity). The hazard ratio (HR) was estimated with a Cox regression model with treatment group as the main effect and stratification factors at randomization as covariates. Kaplan-Meier methods were used to estimate medians and generate survival curves. Results: At a median follow-up of 24.8 months, the addition of relacorilant to nab-paclitaxel resulted in a statistically and clinically significant improvement in OS (HR 0.65; 95% confidence interval [CI], 0.51 to 0.83; P = 0.0004). Median OS in the relacorilant combination arm was extended by 4.1 months compared with the nab-paclitaxel monotherapy arm (16.0 vs 11.9 months). Prior taxane use was almost universal (n = 379/381, 99.5%). A consistent OS benefit was observed irrespective of the taxane-free interval: taxane-free interval ≤6 months (n = 55, HR 0.60 [95% CI, 0.31 to 1.15], median difference 5.7 months) and taxane-free interval > 6 months (n = 324, HR 0.66 [95% CI, 0.51 to 0.86], median difference 3.6 months). Moreover, a consistent OS benefit was observed irrespective of whether a taxane was used in the most recent regimen: taxane in the last regimen (n = 73, HR 0.67 [95% CI, 0.38 to 1.19], median difference 3.9 months) and no taxane in the last regimen (n = 308, HR 0.63 [95% CI, 0.48 to 0.82], median difference 4.2 months). Additional safety data will be presented. Conclusions: ROSELLA met both dual primary endpoints. Relacorilant plus nab-paclitaxel demonstrated a statistically and clinically significant OS benefit in patients with PROC compared to a weekly taxane, the most efficacious chemotherapy. Subgroup analyses for OS showed a consistent benefit favoring the addition of relacorilant to nab-paclitaxel irrespective of prior taxane use. Clinical trial information: NCT05257408 .

Screening and trends: A Global Burden of Disease 2023 assessment of colorectal cancer mortality across G7 nations.

3656 Background: Historically, the adoption of screening techniques has led to a steady decline in colorectal carcinoma (CRC) mortality in high-income countries. However, recent epidemiological data points towards a potential saturation of screening benefits and a rising burden of early-onset disease. Using Global Burden of Disease (GBD) 2023 data, we were able to identify points of stagnation and trend reversals in CRC mortality rates for G7 nations and hypothesize a systemic screening saturation in the post-pandemic era. Methods: The Global Burden of Disease 2023 study was used to retrieve data that included age-standardized death rates (ASDR) for G7 nations (2000-2023). Trends were analyzed using the Joinpoint regression Program, Version 5.4.0.0. We employed a log-linear model to estimate Annual Percent Change (APC). Pairwise comparison tests assessed parallelism between national trajectories to identify statistically distinct trend patterns. Results: From 2000 to 2023, epidemiological data shows an overall decline in the age standardized death rates (ASDR) for colorectal carcinoma in the USA. The ASDR in 2000 was 18.54 (95% UI: 16.80-19.87) and in 2023 it decreased to 12.64 (AAPC: -1.66: 95% CI: -1.83 to -1.49). Upon further analysis, three individual trajectory phenotypes were detected across the G7. The USA and Canada displayed a stagnation phenotype, in which mortality rates plateaued in the more modern years after initial rapid declines. In USA 2018-2023 APC was -0.48 (95% CI: -1.03 to 0.08) and in Canada 2020-2023 APC was 0.26 (95% CI: -0.94 to 1.47). The UK, Japan and France exhibited a rather alarming reversal phenotype, where mortality rates significantly accelerated in recent years. In UK 2021-2023 APC was 2.87 (95% CI: 0.74 to 5.06) while Japan 2021-2023 APC was 2.68 (95% CI: 1.45 to 3.93) and France 2021-2023 APC was 2.56 (95% CI: -2.06 to 7.40). Italy, however, has maintained a sustained decline phenotype, which sharply contrasts with that of the aforementioned nations. In Italy 2003-2023 APC was -1.65 (95% CI: -1.74 to -1.56) with no evidence of saturation. Pairwise comparison confirmed that the USA trajectory was significantly non-parallel to Italy (p <0.05). Conclusions: For the majority of G7 nations, the era of universal CRC mortality decline has come to an end. While the USA and Canada show halted progress, the UK, Japan and France show early signs of slope inversion. On the contrary, Italy’s clear lead in maintenance of declining mortality suggests a policy-based limitation as opposed to unavoidable biological circumstances. Urgent implementation of revolutionized screening techniques and interventions, focusing on hard-to screen populations as well as early onset cohorts, are required to avert a global deterioration in CRC outcomes.

Disease kinetics and practice patterns in ≥ 4-year long-term beneficiaries of immune checkpoint inhibitors for advanced non–small cell lung cancer.

8561 Background: Immune checkpoint inhibitors (ICIs) have transformed outcomes in advanced non-small cell lung cancer (NSCLC), enabling durable responses in a subset of patients (pts). However, detailed clinical trajectories and patterns of late disease progression among long-term survivors remain poorly characterized. Methods: This multicenter retrospective cohort study enrolled advanced NSCLC pts who initiated ICI-containing therapy between January 2015 and April 2020. Long-term beneficiaries (LTBs) were defined as pts achieving both overall survival (OS) and time to next cytotoxic chemotherapy (TTNC) ≥4 years (yrs). We performed 4-yr landmark analyses, characterized late progression (defined as the first radiographic progression ≥4 yrs from ICI initiation), and evaluated cause-specific mortality using competing risk analysis. Results: Of 3,144 pts, 537 (17%) survived ≥4 yrs; 295 (9.4%) were LTBs (median follow-up, 68.6 months; only 8.1% lost to follow-up). ICI was initiated as first-line therapy in 186 pts (63.1%) and as second-line or later in 109 pts (36.9%). The median age was 67 yrs, and PD-L1 Tumor Proportion Score ≥50% was observed in 57%. Among 235 LTBs without progression at 4 yrs, 156 (66%) had discontinued ICI. Among pts progression-free at 4 yrs, lung cancer-specific OS (LC-OS) rates from ICI initiation were 97.8% at 6 yrs and 88.0% at 8 yrs (Table). Late progression occurred in 26 of 235 progression-free LTBs (11.1%); all had progression involving ≤5 lesions. The median interval from the last non-progressive assessment to the first assessment meeting radiographic progression was 98 days (IQR, 56–189), with a median sum-of-diameters growth rate of 6.2 mm/month (IQR, 3.4–9.6). Local therapy was selected in 42% after progression. Among 22 deaths occurring ≥4 yrs after ICI initiation, only 7 (32%) were lung cancer–related, whereas 15 (68%) were due to other causes, including five secondary malignancies. Competing risk analysis showed that the cumulative incidence of other-cause death consistently exceeded that of lung cancer death throughout follow-up (lung cancer death: 0.5% at 5 yrs to 10.7% at 8 yrs; other-cause death: 2.3% to 14.8%). Conclusions: LTBs of ICIs achieved durable disease control, with LC-OS approaching 90% at 8 yrs. In these pts, late progression was uncommon, typically involving ≤5 lesions with modest growth kinetics, often treated with local therapy without requiring immediate systemic treatment. The predominance of non-lung cancer mortality suggests that survivorship care addressing second malignancies is increasingly important in this population. Landmark survival analysis from 4 years after ICI initiation (n=235). Timepoint PFS TTNC OS Other Cause OS LC-OS 5-year 90.1% 96.4% 97.2% 97.7% 99.5% 6-year 82.4% 90.3% 91.8% 93.8% 97.8% 7-year 74.6% 81.3% 82.7% 87.3% 94.7% 8-year 69.9% 74.3% 74.5% 84.7% 88.0%